产品说明书

Rucaparib phosphate

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	同义名 :	芦卡帕利 ;PF-01367338 phosphate;AG-014699 phosphate;PF-01367338;AG-014699;Rucaparib (phosphate)
	CAS号 :	459868-92-9
	货号 :	A424427
	分子式 :	C₁₉H₂₁FN₃O₅P
	纯度 :	99%+
	分子量 :	421.359
	MDL号 :	MFCD17010269
	存储条件：	粉末 Sealed in dry,Room Temperature 液体 -20°C:3-6个月-80°C:12个月
	溶解度 :	DMSO: 35 mg/mL(83.06 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO H₂O: 5 mg/mL(11.87 mM)，配合低频超声，并水浴加热至45℃助溶
	动物实验配方：	IP 2% DMSO+water 9 mg/mL clear PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点	PARP PARP, Ki:1.4 nM
描述	PARP1, also called as Poly (ADP-ribose) polymerase, is involved in the signaling of DNA damage. It can recognize and bind DNA single or double-strand breaks, thus possessing various cellular function, including regulation of apoptosis and chromosome stability, gene amplification and transcription, as well as cell division and differentiation. Rucaparib Phosphate is a potent PARP inhibitor with Ki value of 1.4 nM (measured by enzyme assays)^[1]. Rucaparib Phosphate at dose ranging in 1-10 μM can suppress the level of PAR, as well as induce γ-H2AX, formation and PARP cleavage in a dose-dependent manner indicative of DNA damage and apoptosis, respectively, in MDA-MB468, MDA-MB-231, and Cal-51 cells in the presence of 5% FBS-supplemented DMEM medium for 72 h. Rucaparib Phosphate at concentrations >2.5 μM decreased the p-Stat3 in MDA-MB-468 and MDA-MB-231, as well as dose-dependently increased the p-Akt-S473 in MDA-MB-468 and Cal-51 cells^[2]. Rucaparib Phosphate can chemosensitize neuroblastoma cell lines to temozolomide or topotecan in vitro and in vivo. Rucaparib Phosphate at concentration of 0.4 μM caused a significant sensitization of topotecan (1-30 nM) and temozolomide (1-200 μM) in NB-1691, SH-SY-5Y and SKNBE(2c) cells. Rucaparib Phosphate (1 mg/kg) increased the temozolomide-induced (68 mg/kg) tumor growth delay by 50% (to >89 days) and complete and increased the number of mice with complete and persistent tumor regressions (‎≥ 100 days). Co-administration of Rucaparib Phosphate (1 mg/kg) with topotecan (1 mg/kg) increased total number of complete regressions^[3].
作用机制	Rucaparib Phosphate can compete with NAD⁺ for the PARP catalytic site^[4]

细胞研究
细胞系	浓度	检测类型	检测时间	活动说明	数据源
A2780		Growth Inhibition Assay		IC50=3.94 ± 0.25 μM	23729402
A549	400 nM	Growth Inhibition Assay	24 h	increases cellular radiosensitivity	24411611
AU565	500 nM	Growth Inhibition Assay	10–15 d	reduces cell growth in the four lines and significantly	25128455

实验方案

1mg

5mg

10mg

1 mM

5 mM

10 mM

2.37mL

0.47mL

0.24mL

11.87mL

2.37mL

1.19mL

23.73mL

4.75mL

2.37mL

参考文献

[1]Thomas HD, Calabrese CR, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther. 2007 Mar;6(3):945-56.

[2]Chuang HC, Kapuriya N, et al. Differential anti-proliferative activities of poly(ADP-ribose) polymerase (PARP) inhibitors in triple-negative breast cancer cells. Breast Cancer Res Treat. 2012 Jul;134(2):649-59.

[3]Daniel RA, Rozanska AL, et al. Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. Clin Cancer Res. 2009 Feb 15;15(4):1241-9.

[4]Javle M, Curtin NJ, et al. The potential for poly (ADP-ribose) polymerase inhibitors in cancer therapy. Ther Adv Med Oncol. 2011 Nov;3(6):257-67.

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靶点

靶点	数值

PARP	PARP, Ki:1.4 nM